scholarly journals Kinetics of Amyloid Formation by Different Proteins and Peptides: Polymorphism and Sizes of Folding Nuclei of Fibrils

10.5772/63359 ◽  
2016 ◽  
Author(s):  
Oxana V. Galzitskaya ◽  
Nikita V. Dovidchenko ◽  
Olga M. Selivanova
Keyword(s):  
Amyloid Formation ◽  
Kinetics Of ◽  
Proteins And Peptides

scholarly journals Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation

2006 ◽  
Vol 87 (8) ◽  
pp. 2443-2449 ◽  
Author(s):  
Patrick A. Lewis ◽  
M. Howard Tattum ◽  
Samantha Jones ◽  
Daljit Bhelt ◽  
Mark Batchelor ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Amyloid Formation ◽  
Native Structure ◽  
Prion Strain ◽  
Profound Influence ◽  
Human Prion Protein ◽  
Kinetics Of ◽  
Codon 129

The human prion protein (PrP) has a common polymorphism at residue 129, which can be valine or methionine. This polymorphism has a strong influence on susceptibility to prion diseases and on prion-strain properties. Previous work has shown that this amino acid variation has no measurable effect on the native structure of cellular PrP (PrPC). Here, it is shown that the polymorphism does not change the efficiency of conversion to the β-PrP conformation or affect the binding of copper(II) ions. However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously.

scholarly journals Insights into the Structure of Amyloid Fibrils

2009 ◽  
Vol 2 (1) ◽  
pp. 185-192
Author(s):  
Karen E. Marshall ◽  
Louise C. Serpell
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Formation ◽  
X Ray Diffraction ◽  
Generic Structure ◽  
Structural Characterisation ◽  
Cryo Electron Microscopy ◽  
Atomic Interactions ◽  
Heterogeneous Nature ◽  
Structural Insights ◽  
Proteins And Peptides

Various proteins and peptides are able to self assemble into amyloid fibrils that are associated with disease. Structural characterisation of these fibres is limited by their insoluble and heterogeneous nature. However, advances in various techniques including X-ray diffraction, cryo-electron microscopy and solid state NMR have provided detailed information on various amyloid fibrils, from the long range order and macromolecular structure to the atomic interactions that promote assembly and stabilise the amyloid core. The cross-β model has been widely accepted as a generic structure for most amyloid fibrils and is discussed in detail. It is clear, however, that polymorphisms are present, even in fibrils formed from the same precursor protein, and that these may represent differences in packing at a molecular level. To fully understand the roles of particular residues in amyloid formation and structure, short peptides can be used in conjunction with mutagenesis studies to assess their effects. The structural insights gained using a combination of techniques to study both full-length, disease related peptides and short fragments are essential if progress is to be made towards understanding why these fibres form and how to prevent their formation.

scholarly journals The Kinetics of Amyloid Fibril Formation by de Novo Protein Albebetin and Its Mutant Variants

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 241
Author(s):  
Vitalii Balobanov ◽  
Rita Chertkova ◽  
Anna Egorova ◽  
Dmitry Dolgikh ◽  
Valentina Bychkova ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
De Novo ◽  
Point Mutations ◽  
Inhibitory Effect ◽  
Structural Basis ◽  
Amyloid Formation ◽  
Amyloid Fibril Formation ◽  
External Conditions ◽  
New Perspective ◽  
Kinetics Of

Engineering of amyloid structures is one of the new perspective areas of protein engineering. Studying the process of amyloid formation can help find ways to manage it in the interests of medicine and biotechnology. One of the promising candidates for the structural basis of artificial functional amyloid fibrils is albebetin (ABB), an artificial protein engineered under the leadership of O.B. Ptitsyn. Various aspects of the amyloid formation of this protein and some methods for controlling this process are investigated in this paper. Four stages of amyloid fibrils formation by this protein from the first non-fibrillar aggregates to mature fibrils and large micron-sized complexes have been described in detail. Dependence of albebetin amyloids formation on external conditions and some mutations also have been described. The introduction of similar point mutations in the two structurally identical α-β-β motifs of ABB lead to different amiloidogenesis kinetics. The inhibitory effect of a disulfide bond and high pH on amyloid fibrils formation, that can be used to control this process, was shown. The results of this work are a good basis for the further design and use of ABB-based amyloid constructs.

scholarly journals Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies

2015 ◽  
Vol 1 (7) ◽  
pp. e1500137 ◽  
Author(s):  
Shira Shaham-Niv ◽  
Lihi Adler-Abramovich ◽  
Lee Schnaider ◽  
Ehud Gazit
Keyword(s):  
Metabolic Disorders ◽  
Amyloid Fibrils ◽  
Metabolic Diseases ◽  
Apoptotic Cell ◽  
Single Amino Acid ◽  
Amyloid Formation ◽  
Mice Model ◽  
General Phenomenon ◽  
New Paradigm ◽  
Proteins And Peptides

The accumulation of amyloid fibrils is the hallmark of several major human diseases. Although the formation of these supramolecular entities has previously been associated with proteins and peptides, it was later demonstrated that even phenylalanine, a single amino acid, can form fibrils that have amyloid-like biophysical, biochemical, and cytotoxic properties. Moreover, the generation of antibodies against these assemblies in phenylketonuria patients and the correlating mice model suggested a pathological role for the assemblies. We determine that several other metabolites that accumulate in metabolic disorders form ordered amyloid-like ultrastructures, which induce apoptotic cell death, as observed for amyloid structures. The formation of amyloid-like assemblies by metabolites implies a general phenomenon of amyloid formation, not limited to proteins and peptides, and offers a new paradigm for metabolic diseases.

scholarly journals The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthias M. Schneider ◽  
Saurabh Gautam ◽  
Therese W. Herling ◽  
Ewa Andrzejewska ◽  
Georg Krainer ◽  
...  
Keyword(s):  
Molecular Chaperones ◽  
De Novo ◽  
Cellular Protein ◽  
Amyloid Formation ◽  
First Order ◽  
Hsp70 Family ◽  
First Order Kinetics ◽  
Reaction Proceeds ◽  
Kinetics Of

AbstractMolecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson’s disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies.

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